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Articles 1 - 12 of 12
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou
The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou
Doctoral Dissertations
Candida albicans phosphatidylserine (PS) synthase, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals against systemic candidiasis due to its importance in virulence, absence in the host and conservation among fungal pathogens. This dissertation is focused on the identification of inhibitors for this membrane enzyme. Cho1 has two substrates: cytidyldiphosphate-diacylglycerol (CDP-DAG) and serine. Previous studies identified a conserved CDP-alcohol phosphotransferase (CAPT) binding motif present within Cho1, and here we revealed that mutations in all but one conserved amino acid within the CAPT motif resulted in decreased Cho1. For serine, we have predicted a …
Characterization Of Lignin Structural Variability And The Associated Application In Genome Wide Association Studies, Nathan D. Bryant
Characterization Of Lignin Structural Variability And The Associated Application In Genome Wide Association Studies, Nathan D. Bryant
Doctoral Dissertations
Poplar (Populus sp.) is a promising biofuel feedstock due to advantageous features such as fast growth, the ability to grow on marginal land, and relatively low lignin content. However, there is tremendous variability associated with the composition of biomass. Understanding this variability, especially in lignin, is crucial to developing and implementing financially viable, integrated biorefineries. Although lignin is typically described as being comprised of three primary monolignols (syringyl, guaiacyl, p-hydroxyphenyl), it is a highly irregular biopolymer that can incorporate non-canonical monolignols. It is also connected by a variety of interunit linkages, adding to its complexity. Secondary cell wall …
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Doctoral Dissertations
Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …
Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff
Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff
Doctoral Dissertations
The endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat …
Atomistic Simulations Of Intrinsically Disordered Protein Folding And Dynamics, Xiping Gong
Atomistic Simulations Of Intrinsically Disordered Protein Folding And Dynamics, Xiping Gong
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) are crucial in biology and human diseases, necessitating a comprehensive understanding of their structure, dynamics, and interactions. Atomistic simulations have emerged as a key tool for unraveling the molecular intricacies and establishing mechanistic insights into how these proteins facilitate diverse biological functions. However, achieving accurate simulations requires both an appropriate protein force field capable of describing the energy landscape of functionally relevant IDP conformations and sufficient conformational sampling to capture the free energy landscape of IDP dynamics. These factors are fundamental in comprehending potential IDP structures, dynamics, and interactions. I first conducted explicit solvent simulations to …
A Shift In Rna Fate: Investigating The Role Of C19orf66 During Kshv Lytic Replication, William Rodriguez Jr.
A Shift In Rna Fate: Investigating The Role Of C19orf66 During Kshv Lytic Replication, William Rodriguez Jr.
Doctoral Dissertations
During viral infection, virus and host clash for control of the cell in a conflict that ultimately drives the evolution of both sides and has lasting consequences in the form of pathogenesis. At the heart of this struggle is a contest for control of cellular gene expression, a struggle epitomized by an evolutionary tug-of-war for supremacy over RNA fate. During lytic replication, Kaposi’s sarcoma-associated herpesvirus (KSHV) triggers a massive RNA decay event known as viral “Host Shutoff” which decimates greater than 70% of the host transcriptome, simultaneously suppressing the cellular anti-viral response and freeing host resources for viral replication. However, …
Role Of Fat Content On The Structure And Function Of Human Skeletal Muscle, Joseph A. Gordon Iii
Role Of Fat Content On The Structure And Function Of Human Skeletal Muscle, Joseph A. Gordon Iii
Doctoral Dissertations
Muscle size does not fully explain variations in muscle strength. Fat content has been implicated in muscle weakness, though this relationship remains unclear. The relationship between fat and strength may vary between scales (e.g., cellular, organ, and organism). The goal of this dissertation was to clarify the role of fat in the structure and function of muscle using in vitro and in vivo techniques across multiple scales in adults 21-45 years old. Study 1 tested the agreement of intramyocellular lipid (IMCL) content between oil red o (ORO) and magnetic resonance spectroscopy (MRS) techniques. These measures of IMCL were also compared …
Cell-Free Metabolic Engineering Strategies For Accelerated Biomanufacturing, Jaime Lorenzo N. Dinglasan
Cell-Free Metabolic Engineering Strategies For Accelerated Biomanufacturing, Jaime Lorenzo N. Dinglasan
Doctoral Dissertations
Biomanufacturing propels the bioeconomy. Accelerating bioeconomic growth thus requires the expedited development of biomanufacturing processes that can expand the current bioproduct portfolio. Lysate-based cell-free systems provide unique advantages for simplified metabolic pathway construction. Their central metabolic pathways and transcriptional-translational (TX-TL) machineries are free from genome regulation and are amenable to direct manipulation, enabling the streamlined construction of biomanufacturing processes. While their utility as prototyping platforms for accelerating cellular metabolic engineering has been demonstrated, the potential to rapidly build commercial “cell-free factories” capable of sophisticated bioconversion has not been fully realized. Lysates with high-yield pathways are projected to enable commercialized cell-free …
The Development Of Tailored Amphiphilic Copolymers For Detergent-Free Integral Membrane Protein Extraction, Cameron Edward Workman
The Development Of Tailored Amphiphilic Copolymers For Detergent-Free Integral Membrane Protein Extraction, Cameron Edward Workman
Doctoral Dissertations
Integral membrane proteins are prolific targets for the design, development, and delivery of pharmaceuticals. In fact, over 60% of all currently available drugs target these proteins to accomplish their therapeutic effect. However, integral membrane proteins remain the least characterized class of all proteins, accounting for only ~2% of all solved protein structures. One of the primary reasons for this low number of solved protein structures is that many membrane proteins lose their native conformation when extracted using conventional methods (e.g. detergents), convoluting accurate structure determination. In contrast, amphiphilic styrene-maleic acid copolymers (SMAs) were recently discovered to readily isolate membrane proteins …
Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage
Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage
Doctoral Dissertations
RNA is poised to revolutionize medicine. By simply changing the sequence, one therapeutic can be converted into a wholly new one, with little or no change in manufacturing and formulation. While a single mRNA vaccine produced at massive scale can treat billions, the re-codability of RNA will also enable the widespread growth of personalized medicines. T7 RNA polymerase is highly efficient at the synthesis of therapeutic RNA, but is known to produce unintended RNA impurities during synthesis. These products arise from the encoded RNA rebinding the enzyme such that its 3’ end serves as a primer for extension. This leads …
Modulation Of Plant Immunity During The Establishment Of The Nitrogen-Fixing Symbiosis, Miriam Hernandez-Romero
Modulation Of Plant Immunity During The Establishment Of The Nitrogen-Fixing Symbiosis, Miriam Hernandez-Romero
Doctoral Dissertations
Nitrogen is essential for plant tissue growth but is often a limited resource in soils. Many legumes overcome this limitation by entering a symbiotic association with soil microbes, called rhizobia, which provide nitrogen to the plant while rhizobia receive fixed carbon. To successfully form a symbiosis, the host and symbiont exchange a series of molecular signals. One major obstacle during this interaction is the host's innate immune system, which becomes active upon rhizobial detection. It is therefore the main focus of this thesis to identify the mechanisms that modulate host immunity. In the subsequent chapters, we focus on a rhizobial …
Characterizing The Roles Of The Variable Linker And Hub Domains In Camkii Activation, Noelle Dziedzic
Characterizing The Roles Of The Variable Linker And Hub Domains In Camkii Activation, Noelle Dziedzic
Doctoral Dissertations
Learning and memory formation at the cellular level involves decoding complex electrochemical signals between nerve cells, or neurons. Understanding these processes at the molecular level requires a comprehensive study of calcium-sensitive proteins that serve as signal mediators within cells. More specifically, the protein calcium/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of downstream cellular signaling events in the brain, playing an important role in long term memory formation. CaMKII is encoded in humans on four different genes: alpha, beta, gamma and delta. For added complexity, each of these gene products can be alternatively spliced and translated into multiple protein …